This is a second revised application for an exploratory/developmental research grant award (R21). Positive social relationships have consistently been associated with better health, although the neurobiological underpinnings of these observed effects are not well understood. Valuable insight may be gained by a life course perspective as it is becoming increasingly apparent that early life social experiences are crucially related to later life functioning and well-being. The overall goal of the proposed work is to explore novel biological pathways that may help to explain how social relationships influence health throughout the life course. Oxytocin is a neurohypophyseal hormone hypothesized to coordinate both the causes and effects of positive social interactions, and may be involved in positive physiological adaptations such as buffering the deleterious effects of stress. The proposed research will examine whether and how oxytocin influences responses to stress in humans and will consider these effects in relation to those of social support. More specifically, experimental research will be used to determine whether exogenously administered oxytocin (intranasal) influences psychological and physiological outcomes under conditions of stress across gender and age in adulthood. Hypotheses to be tested are: 1) Oxytocin ameliorates the deleterious neuroendocrine, cardiovascular, and subjective effects of stress;2) Oxytocin and social support have similar and additive stress-buffering effects;3) Effects of oxytocin are stronger in women versus men;4) Effects of oxytocin are similar across a range of both younger and older adult ages. Hypotheses will be tested with a placebo-controlled double blind study using a sample of healthy men and women recruited from the community. Participants will be randomly assigned to receive either oxytocin or placebo. They will undergo a social stress manipulation with and without social support (randomly assigned), and outcome measures will be obtained at multiple times during the procedure. The proposed research represents a novel area of investigation by a multidisciplinary team of investigators. This work will provide a solid platform from which to launch a larger program of research aimed at identifying how positive social and emotional experiences influence adult health and longevity. Ultimately, a more neurobiological understanding of resilience can inform efforts for prevention and intervention of diseases or problems common in later life. PUBLIC HEALTH RELEVANCE: The proposed work has the potential to provide new insight into the biological mechanisms underlying the protective effects of positive social relationships on health. This experimental study utilizes a multidisciplinary approach focusing on the interplay between molecular, psychological, and social processes as they relate to aging, and will provide a solid platform from which to launch a larger program of research. Ultimately, a neurobiological understanding of resilience may inform efforts for both prevention and intervention of diseases or problems common in later life.